目的 以中醫(yī)“異病同治”理論為依據(jù)，采用網(wǎng)絡(luò)藥理學(xué)與分子對(duì)接方法探討化肝煎“異病同治”失眠、慢性萎縮性胃炎和胃食管反流病的作用靶點(diǎn)及可能作用機(jī)制。方法 通過中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺(tái)（TCMSP）等中藥化合物數(shù)據(jù)庫結(jié)合文獻(xiàn)挖掘獲取化肝煎的化學(xué)成分和作用靶點(diǎn)；結(jié)合GeneCards、OMIM、PharmGKB、DRUGBANK、TTD數(shù)據(jù)庫獲取化肝煎治療失眠、慢性萎縮性胃炎和胃食管反流病的作用靶點(diǎn)。采用Cytoscape軟件繪制化肝煎中藥-成分-靶點(diǎn)網(wǎng)絡(luò)，利用Venny軟件得出相關(guān)交集基因?；贑ytoscape軟件繪制化肝煎-成分-靶點(diǎn)可視化網(wǎng)絡(luò)圖，借助STRING數(shù)據(jù)庫及Cytoscape軟件構(gòu)建蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)，分析獲得核心作用靶點(diǎn)。采用Metascape平臺(tái)工具對(duì)其進(jìn)行基因本體論（GO）注釋及京都基因與基因組百科全書（KEGG）通路富集分析。使用AutodockTools軟件對(duì)化肝煎主要活性成分與疾病作用靶點(diǎn)進(jìn)行分子對(duì)接。結(jié)果 篩選得到化肝煎化學(xué)成分56個(gè)，疾病靶點(diǎn)：失眠438個(gè)，慢性萎縮性胃炎868個(gè)，胃食管反流病4 252個(gè)，以及20個(gè)藥物成分和疾病共同靶點(diǎn)。PPI網(wǎng)絡(luò)中關(guān)鍵蛋白排名靠前的靶點(diǎn)為IL6、NCF1、PTGS2、CRP、MPO、PPARG、TNF等。獲得GO富集分析結(jié)果排名靠前的有452種生物過程（BP）、19種分子功能（MF）、6種細(xì)胞組分（CC），KEGG信號(hào)通路主要有6條信號(hào)通路。分子對(duì)接結(jié)果顯示關(guān)鍵成分與對(duì)應(yīng)靶點(diǎn)具有較好的結(jié)合活性。結(jié)論 化肝煎治療失眠、慢性萎縮性胃炎和胃食管反流病可能涉及TNF、IL6、PTGS2、PPARG、CRP等為代表的核心靶點(diǎn)，其實(shí)現(xiàn)異病同治的作用可能與脂質(zhì)信號(hào)通路調(diào)控炎癥、細(xì)胞因子反應(yīng)等有關(guān)。

Objective Based on the theory of "treating the different diseases with the same therapy" in traditional Chinese medicine, network pharmacology and molecular docking method were used to explore the target and possible mechanism of Hua-Gan Decoction (HGD) "treating the different diseases with the same therapy" in insomnia, chronic atrophic gastritis and gastroesophageal reflux disease. Methods The chemical constituents and action targets of HGD were obtained by TCMSP and literature mining. Combined with GeneCards, OMIM, PharmGKB, DRUGBANK and TTD database, the therapeutic targets of HGD for insomnia, chronic atrophic gastritis and gastroesophageal reflux disease were obtained. Cytoscape software was used to draw the "TCMcomponent-target" network of gain, and the related intersection genes were obtained by Venny software. Based on Cytoscape software, a visual network map of "HGD-component-target" was drawn, and a PPI network was constructed with the help of STRING database and Cytoscape software to analyze and obtain the core targets. The Metascape platform tool was used for GO enrichment analysis and KEGG pathway analysis. AutodockTools were used to conduct molecular docking between the main active ingredients of HGD and the disease targets. Results A total of 56 chemical components of HGD, 438 disease targets of insomnia, 868 chronic atrophic gastritis, 4 252 gastroesophageal reflux disease and 20 common targets of drug components and diseases were screened. The top targets of key proteins in PPI network were IL6, NCF1, PTGS2, CRP, MPO, PPARG, TNF, etc. GO enrichment analysis results were obtained for 452 biological processes, 19 molecular functions and six cellular components, and KEGG signaling pathways mainly included six signaling pathways. The molecular docking results showed that the key components had good binding activity with corresponding targets. Conclusion HGD may involve the core targets represented by TNF, IL6, PTGS2,PPARG and CRP in the treatment of insomnia, chronic atrophic gastritis and gastroesophageal reflux disease, and its effect on the simultaneous treatment of different diseases may be related to the regulation of lipid signaling pathway in inflammation and cytokine response.

R285.5

國家重點(diǎn)研發(fā)計(jì)劃項(xiàng)目（2017YFC1700601）；"十三五"國家重點(diǎn)研發(fā)計(jì)劃中醫(yī)藥現(xiàn)代化研究專項(xiàng)（2017YFC1703703）；陜西省特支計(jì)劃科技創(chuàng)新領(lǐng)軍人才項(xiàng)目（646）